Fruits and barks extracts of Zanthozyllum heitzii a spice from Cameroon induce mitochondrial dependent apoptosis and Go/G1 phase arrest in human leukemia HL-60 cells

BACKGROUND: Zanthoxylum heitzii is a spice used to prepare several dishes and to treat tumors, syphilis, malaria, cardiac palpitations, urogenital infections in the west region of Cameroon, but the antitumor mechanisms and chemical composition are not yet investigated. This study was aimed to determ...

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Autores principales:	Pieme,Constant Anatole, Santosh,Guru Kumar, Tekwu,Emmanuel Mouafo, Askun,Tülin, Aydeniz,Hatice, Ngogang,Jeanne Yonkeu, Bhushan,Shashi, Saxena,Ajit Kumar
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2014
Materias:	Zanthozyllum heitzii Syringic acid Apoptosis HL-60 cells ROS Mitochondrial membrane potential
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602014000100048
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spelling	oai:scielo:S0716-976020140001000482015-10-30Fruits and barks extracts of Zanthozyllum heitzii a spice from Cameroon induce mitochondrial dependent apoptosis and Go/G1 phase arrest in human leukemia HL-60 cellsPieme,Constant AnatoleSantosh,Guru KumarTekwu,Emmanuel MouafoAskun,TülinAydeniz,HaticeNgogang,Jeanne YonkeuBhushan,ShashiSaxena,Ajit Kumar Zanthozyllum heitzii Syringic acid Apoptosis HL-60 cells ROS Mitochondrial membrane potential BACKGROUND: Zanthoxylum heitzii is a spice used to prepare several dishes and to treat tumors, syphilis, malaria, cardiac palpitations, urogenital infections in the west region of Cameroon, but the antitumor mechanisms and chemical composition are not yet investigated. This study was aimed to determine the antiproliferative effects of four extracts from the fruits and barks of Zanthoxyllum heitzii (Rutaceae) on apoptosis in human promyelocytic cells, their mechanisms and the chemical composition. The 3-(4, 5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the fifty percent inhibition (IC50) concentration of the cell lines after treatment. The effect on morphology was observed using a light or fluorescence microscopy. The rate of apoptosis and the cell cycle were measured using flow cytometry (FCM). The phytochemical analysis of the extract was carried with HPLC/MS methods. RESULTS: The phytochemical analysis of the extracts indicated the presence of four known polyphenols (Syringic acid, Juglon, Luteolin and Myricetin) in both fruits and barks of Z. heitzii but in different quantities. Syringic acid and Myricetin concentrations were between 17-21 fold higher in the fruits than the stem bark. Rhamnetin (393.35 μg/mL) and Oleuropein (63.10 μg/mL) were identified only in the stem barks of Z. heitzii. Among the four extracts tested for cytotoxicity properties, only the methanol extract of fruits and barks significantly inhibited cell proliferation of HL-60 cells with IC50 value of 20 μg/mL and 12 μg/mL respectively. HL-60 cells treated with Z. heitzii extracts significantly produced reactive oxygen species (ROS) with concurrent loss of mitochondrial membrane potential (MMP). Modifications in the DNA distribution and enhanced of G1/G0 phase cell cycle arrest were observed in a concentration dependent manner. CONCLUSIONS: Polyphenols from Z. heitzii plant exert inhibitory effect on HL-60 cells through the reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and cell cycle destabilization.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.47 20142014-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602014000100048en10.1186/0717-6287-47-54
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Zanthozyllum heitzii Syringic acid Apoptosis HL-60 cells ROS Mitochondrial membrane potential
spellingShingle	Zanthozyllum heitzii Syringic acid Apoptosis HL-60 cells ROS Mitochondrial membrane potential Pieme,Constant Anatole Santosh,Guru Kumar Tekwu,Emmanuel Mouafo Askun,Tülin Aydeniz,Hatice Ngogang,Jeanne Yonkeu Bhushan,Shashi Saxena,Ajit Kumar Fruits and barks extracts of Zanthozyllum heitzii a spice from Cameroon induce mitochondrial dependent apoptosis and Go/G1 phase arrest in human leukemia HL-60 cells
description	BACKGROUND: Zanthoxylum heitzii is a spice used to prepare several dishes and to treat tumors, syphilis, malaria, cardiac palpitations, urogenital infections in the west region of Cameroon, but the antitumor mechanisms and chemical composition are not yet investigated. This study was aimed to determine the antiproliferative effects of four extracts from the fruits and barks of Zanthoxyllum heitzii (Rutaceae) on apoptosis in human promyelocytic cells, their mechanisms and the chemical composition. The 3-(4, 5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the fifty percent inhibition (IC50) concentration of the cell lines after treatment. The effect on morphology was observed using a light or fluorescence microscopy. The rate of apoptosis and the cell cycle were measured using flow cytometry (FCM). The phytochemical analysis of the extract was carried with HPLC/MS methods. RESULTS: The phytochemical analysis of the extracts indicated the presence of four known polyphenols (Syringic acid, Juglon, Luteolin and Myricetin) in both fruits and barks of Z. heitzii but in different quantities. Syringic acid and Myricetin concentrations were between 17-21 fold higher in the fruits than the stem bark. Rhamnetin (393.35 μg/mL) and Oleuropein (63.10 μg/mL) were identified only in the stem barks of Z. heitzii. Among the four extracts tested for cytotoxicity properties, only the methanol extract of fruits and barks significantly inhibited cell proliferation of HL-60 cells with IC50 value of 20 μg/mL and 12 μg/mL respectively. HL-60 cells treated with Z. heitzii extracts significantly produced reactive oxygen species (ROS) with concurrent loss of mitochondrial membrane potential (MMP). Modifications in the DNA distribution and enhanced of G1/G0 phase cell cycle arrest were observed in a concentration dependent manner. CONCLUSIONS: Polyphenols from Z. heitzii plant exert inhibitory effect on HL-60 cells through the reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and cell cycle destabilization.
author	Pieme,Constant Anatole Santosh,Guru Kumar Tekwu,Emmanuel Mouafo Askun,Tülin Aydeniz,Hatice Ngogang,Jeanne Yonkeu Bhushan,Shashi Saxena,Ajit Kumar
author_facet	Pieme,Constant Anatole Santosh,Guru Kumar Tekwu,Emmanuel Mouafo Askun,Tülin Aydeniz,Hatice Ngogang,Jeanne Yonkeu Bhushan,Shashi Saxena,Ajit Kumar
author_sort	Pieme,Constant Anatole
title	Fruits and barks extracts of Zanthozyllum heitzii a spice from Cameroon induce mitochondrial dependent apoptosis and Go/G1 phase arrest in human leukemia HL-60 cells
title_short	Fruits and barks extracts of Zanthozyllum heitzii a spice from Cameroon induce mitochondrial dependent apoptosis and Go/G1 phase arrest in human leukemia HL-60 cells
title_full	Fruits and barks extracts of Zanthozyllum heitzii a spice from Cameroon induce mitochondrial dependent apoptosis and Go/G1 phase arrest in human leukemia HL-60 cells
title_fullStr	Fruits and barks extracts of Zanthozyllum heitzii a spice from Cameroon induce mitochondrial dependent apoptosis and Go/G1 phase arrest in human leukemia HL-60 cells
title_full_unstemmed	Fruits and barks extracts of Zanthozyllum heitzii a spice from Cameroon induce mitochondrial dependent apoptosis and Go/G1 phase arrest in human leukemia HL-60 cells
title_sort	fruits and barks extracts of zanthozyllum heitzii a spice from cameroon induce mitochondrial dependent apoptosis and go/g1 phase arrest in human leukemia hl-60 cells
publisher	Sociedad de Biología de Chile
publishDate	2014
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602014000100048
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Fruits and barks extracts of Zanthozyllum heitzii a spice from Cameroon induce mitochondrial dependent apoptosis and Go/G1 phase arrest in human leukemia HL-60 cells

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